Effect Of RanBP9Expression On Biology Functions And Anoikis Resistance Of Osteosarcoma Cells

Osteosarcoma (OS) is a primary malignant bone tumor originated in mesenchymaltissue, which usually occurs in children and adolescents, the main site for the onset of longbone metaphysis. In the early, the patients didn’t have obvious clinical symptoms and highincidence rate of lung metastasis cause the poor prognosis of this malignant tumor. Themain treatment for OS is chemotherapy, but chemoresistance is the major factor to influencechemotherapeutic effects in both primary and metastatic lesions. With the development ofgene therapy in recent years, it was discovered that the gene expression in OS not onlydetermine their occurrence, development and prognosis, but also affect the treatment, how tofind a new gene target become a hot research in osteosarcoma.RanBP9is a microtubule organization center binding protein with Ran protein, whichparticipate in microtubule nucleation. RanBP9was found expressed in different tissues andcell lines, as a scaffold protein interacts with a variety of receptor proteins which involvedintracellular signal transduction pathways. For example, RanBP9is involved in theregulation of cell cycle and the influence of cell apoptosis by adjusting proapoptotic activity.RanBP9aslo effect the nervous system and the reproductive system, initiate the immuneresponse. It suggests that RanBP9has a potent tumor-suppressor role which can inhibitprotein ubiquitination.Our study includes three successive parts. The first part was to identify the expressionof RanBP9in osteosarcoma tissues and different osteosarcoma cell lines byimmunochemical assay, Real-time PCR, immunofluorescence and Western blot. The secondpart was executed a series of biological tests using in osteosarcoma SaOS2cell line withdown-regulated RanBP9to explain its biological functions in vitro and in vivo. The thirdpart was to set up anoikis-resistant osteosarcoma cell model and to discuss the role ofRanBP9underlying anoikis resisitance and metastasis of osteosarcoma. The main results and conclusions are as follows:1. RanBP9is highly expressed in human osteosarcoma tissues and cell lines, suggestingthe expression of RanBP9was negatively correlated with the degree of malignant.RanBP9may be involved in the occurrence of OS.2. Low expression of RanBP9increased proliferation and reduced apoptosis, whichsuggests that RanBP9may be played an important role during OS development andprogression.3. RanBP9gradual downregulation was accompanied with gradual enhanced anoikisresistance and low expression of RanBP9increased the metastasis, indicate that RanBP9may participate in the regulation of the process of cell anoikis, affect the metastasis of OS.In summary, RanBP9is highly expressed in human osteosarcoma tissues and cell lines.Low expression of RanBP9reduced apoptosis and increased proliferation, as well asincreased the metastasis. It suggests RanBP9has a potent tumor-suppressor role likely inosteosarcoma.